The myocardial cell and its microvascular bed will be explored in order to 1) define the effects and interactions of aging and hypertension, and 2) establish the long-term effects of antihypertensive drug therapy and the regression of cardiac hypertrophy. Comparisons between the Wistar-derived Okamoto-Aoki strain of spontaneously hypertensive rats (SHR) and their normotensive Kyoto-Wistar controls will be made at various ages during their life-span. The experiments by incorporating various morphological and physiological approaches, are designed to correlate structural and functional parameters. Using electron microscopy in conjunction with quantitative methods we hope to define the sequence and magnitude of changes in cellular organelles and inclusions concerned with various aspects of cell function. The role of the extracellular space and its relationship with the transverse tubular system, intercalated disc, sarcolemmal vesicles and the sarcolemma will be investigated with electron microscopy and cytochemistry. As a corollary, histochemistry and histology will be employed to characterize focal and regional alterations indicative of pre-necrotic, necrotic and hypoxic states which may be related to specific cellular changes. The capillary bed will be explored with reference to quantitative morphology, blood flow, permeability and vesicular transport in order to define specific functional and structural parameters which may contribute to regressive changes in the myocardial cell. BIBLIOGRAPHIC REFERENCE: Lund, D.D., R.J. Tomanek and J.W. Davis. Cellular and subcellular basis of cardiac hypertrophy in the spontaneously hypertensive rat, in Spontaneous Hypertension: Its Pathogenesis and Complications (11) in press, 1976.